基于网络药理学的黄连总生物碱防治糖尿病的作用机制研究  

Study on the Action Mechanism of Coptidis Rhizoma Total Alkaloids in Preventing and Treating Diabetes Based on Network Pharmacology

作　　者：邵君傲 李佳川 顾健 史志龙 SHAO Jun-ao;LI Jia-chuan;GU Jian;SHI Zhi-long(College of Pharmacy,Southwest University for Nationalities,Chengdu 610041,China;School of Basic Medicine and Forensic Medicine,West China University of Sichuan,Chengdu 610041,China)

机构地区：[1]西南民族大学药学院,四川成都610041 [2]四川大学华西基础医学与法医学院,四川成都610041

出　　处：《中药材》2019年第6期1374-1379,共6页Journal of Chinese Medicinal Materials

基　　金：国家自然科学基金(81302912);中国博士后科学基金面上项目(2015M582560);中央高校基本科研业务费专项基金项目(2017NZYQN35);西南民族大学研究生创新型科研项目(CX2016SZ042)。

摘　　要：目的:基于网络药理学相关技术系统研究中药黄连防治糖尿病的主要活性成分及相关靶点通路,为黄连总生物碱防治糖尿病作用机制的揭示提供依据。方法:采用TCMSP数据库、KEGG数据库、MAS 3.0生物分子功能注释系统及ChemMapper数据库等数据库对黄连总生物碱成分进行系统分析,同时结合Lipinski类药性五原则筛选出黄连的主要药效成分,筛选相关靶点信息,靶点信息通过MAS 3.0系统完成基因功能和通路注释分析,并运用Cytoscape v3.6.1制作化合物-靶点-疾病网络模型进行分析。结果:研究共筛选出符合要求的黄连生物碱活性成分6个,模拟预测得到直接或间接与糖尿病相关的靶点累计89个,通路53条。推测出在黄连总生物碱防治糖尿病及其并发症的作用中,总生物碱中化合物小檗碱、黄连碱、小檗红碱、表小檗碱、巴马汀、甲基黄连碱等占据主导地位。这些生物碱成分可能通过协同调节PPAR、PI3K-Akt、GSK-3β、VEGF等信号转导通路从而抑制与糖尿病相关的炎症反应、改善胰岛素抵抗及糖脂代谢、恢复胰岛β细胞功能。结论:基于网络药理学的研究表明,黄连总生物碱通过协同调节与炎症反应、胰岛素抵抗、糖脂代谢、胰岛β细胞功能相关的靶点及通路,综合发挥抗糖尿病作用。Objective:To systemically study the main active components of Coptidis Rhizoma on the prevention and treatment of diabetes and their related targets based on the network pharmacology,in order to provide a basis for revealing the mechanism of action of Coptidis Rhizoma total alkaloids in preventing and treating diabetes.Methods:TCMSP database,KEGG database,MAS 3.0 biomolecular functional annotation system and ChemMapper database were used to systematically analyze the total alkaloid components of Coptidis Rhizoma.At the same time,the main medicinal ingredients of Coptidis Rhizoma were screened by combining the five principles of medicinal properties of Lipinski,relevant target information was screened.The target information was analyzed through the MAS 3.0 system for gene function and pathway annotation.Compound-target-disease network model was made by Cytoscape v3.6.1 for analysis.Results:Six alkaloids from Coptidis Rhizoma were selected.A total of eighty-nine targets and fifty-three pathways directly or indirectly related to diabetes were predicted by simulation.It was speculated that berberine,coptisine,acetamide,epiberberine,palmatine,methyl coptisine were dominant compounds from the total alkaloids in the prevention and treatment of diabetes and its complications.These alkaloid components may synergistically regulate signal transduction pathways such as PPAR,PI3K-Akt,GSK-3βand VEGF to inhibit the diabetesrelated inflammatory responses,improve insulin resistance and glycolipid metabolism,restore isletβcell function of the pancreas.Conclusion:The study based on network pharmacology shows that Coptidis Rhizoma alkaloids play an integrated role in antidiabetes by synergistically regulating targets and pathways related to inflammatory response,insulin resistance,glucose and lipid metabolism and isletβcell function.

关 键 词：黄连总生物碱 网络药理学 糖尿病 作用机制 

分 类 号：R285.5[医药卫生—中药学]